446

viruses, including measles. According to Zhdanov’8 and Simpson and linuma19 common R.N.A. viruses may indeed take up D.N.A. forms in tissue culture, probably by utilising reverse transcriptase systems carried by adventitious leukoviruses, and, further, D.N.A. extracted from such cultures can transmit the original infection. Adams and Be1l2O suggested that subacute sclerosing panencephalitis (S.S.P.E.) arises from a rare co-infection of measles cases with an adventitious reverse-transcriptasecarrying leukovirus followed by transcription of measles virion R.N.A. via m-R.N.A. to a D.N.A. form and the establishment of the D.N.A. as a new infectious entity either as the core of a new slow virus or as a membrane-attached viroid. I suggest that s.A.A. and M.S.A.A. may be R.N.A. viruses related to scrapie and M.S. in the same way-i.e., that they are viruses based on the v-R.M.A. forms of the actual aaiological agents. Although there is as yet little conclusive evidence on the nature of the nucleic-acid core of the scrapie agent itself, theoretical considerations and such practical evidence as there is suggest that the scrapie agent is based on D.N.A.20-22 Adams and Dickinson23 also indicated how the assumption that the aetiological agent of M.S. is a scrapie-like slow virus could account for some of the disease characteristics. This proposition is summarised in the figure. Certainly in scrapie, where the most probable size of the core is between 1 x 105 and 2x 105 daltons, the m-R.M.A. and proteins translated from it must also be small. However, there seems no reason why host macromolecules could not be coopted to build the s.A.A. virion up to the 25+nm size indicated by the filtration data. This must happen in the assembly of the scrapie agent itself since the size, as estimated by filtration data, is in the same range. The experimental data showing that proviral D.N.A. produced by reverse transcription of viral R.N .A. 15 16 could be extracted and used to reinfect new cells with recovery of the original (R.N.A.) virus has already been mentioned. Consequently if the above proposals concerning S.A.A. and M.S.A.A. are correct, it should be possible to passage these viruses with D.N.A. isolated from scrapie or M.S. brain, respectively. If successful, such experiments could provide positive evidence of a viral basis for M.s. However, such work must wait on the establishment of a reliable assay system for M.s.A.A.

miological evidence arising from movement of populations between high and low risk M.S. areas which suggests the involvement of a factor acquired at this age. The hypothesis would also indicate that the relationship between M.s. and scrapie is indeed close, as proposed some years ago, and how, by minor errors of transcription between D.N.A. and R.N.A. forms arising in rare instances, results such as those of Field24 involving the development of scrapie in sheep inoculated with M.s. material might occur. REFERENCES

1.

Carp, R. I., 618.

Licursi,

P.

C., Merz, P. A., Merz, G. S. J. exp. Med. 1972, 136,

2. Brown, P., Gajdusek, D. C. Nature, 1974, 247, 217. 3. McNeil, T. A., Killen, M., Trudgett, A. ibid. 1974, 249, 778.

Koldovsky, U., Koldovsky, P., Henle, G., Henle, W., Ackermann, R, Haase, G. Infect. Immun. 1975, 12, 1355. 5. Henle, G., Koldovsky, U., Koldovsky, R., Henle, W., Ackermann, R., Haase, G. ibid. 1975, 12, 1367. 6. Carp, R. I., Merz, G. S., Licursi, P. C. ibid. 1974, 9, 1011. 7. Warner, H. B., Carp, R. I., Narducci, R. Lancet, 1976, i, 688. 8. Lewin, R. New Sci. March 11, 1976, p. 554. 9. Mims, C. Nature, 1976, 260, 190. 10. Lancet, 1976, i, 459. 11. Licursi, P. C., Merz, P. A., Merz, G. S., Carp, R. I. Infect. Immun. 1972, 6, 370. 12. Carp, R. I., Merz, P. A., Licursi, P. C., Merz, G. S. J. infect. Dis. 1973, 128, 4.

256. 13. Riley, V., Lilly, F., Huerto, E., Bordell, D. Science 1960, 132, 545. 14. Adams, D. H., Field, E. J. J. gen. Virol. 1967, 1, 449. 15. Dickinson, A. G., Taylor, D. M., Fraser, H. Nature, 1974, 248, 510. 16. Haase, A. T., Varmus, H. F. Nature new Biol. 1973, 245, 237. 17. Zhdanov, V. M., Parfanovich, M. I. Arch. ges. Virusforsch. 1974, 45, 215. 18. Zhdanov, V. M. Nature, 1975, 256, 471. 19. Simpson, R. W., Iinuma, M. Proc. natn. Acad. Sci. U.S.A. 1975, 72 3230. 20. Adams, D. H., Bell, T. M. Med. Hypoth. 1976, 2, 55. 21. Adams, D. H. J. Neurochem. 1972, 19, 1869. 22. Adams, D. H. Biochem. Soc. Trans. 1973, 1, 1061. 23. Adams, D. H., Dickinson, J. P. Lancet, 1974, i, 1196. 24. Field, E. J. Int. Rev. exp. Path. 1969, 8, 129.

Methods and Devices USE OF PROGRAMMABLE CALCULATOR TO SOLVE PHYSIOLOGICAL EQUATIONS D. G. Ross

OTHER IMPLICATIONS

The suggestion also carries with it some further possibilities. One of the problems with diseases such as scrapie and M.s. is-how are they transmitted in Nature? It has, for example, proved virtually impossible to transmit scrapie to normal mice by caging then with scrapie-infected mice. Whether s.A.A. (or M.s.A.A.) would be transmitted under these circumstances is not yet known. However, the report that a high proportion of contacts of M.s. patients carry anti-M.s.A.A. antibodies,4 suggests that M.s.A.A. is transmissible without great difficulty. If R.N.A. viruses formed via reverse transcription of slowviral D.N.A. are transmissible by the normal contact routes, the original disease could arise in such individuals after co-infection with an adventitious leukovirus, as suggested for s.s.P.E.14 Such a leukovirus infection in an M.s.A.A.-carrying individual (or vice versa) occurring around the age of puberty might then explain the epide-

H.

J. MANSON

Department of Anœsthesia, Aberdeen Royal Infirmary, Aberdeen THE introduction of miniaturised integrated semiconductor circuitry has permitted the development of small electronic calculators.Cheap calculators are now available which can be programmed with keyed-in steps to perform complex mathematical procedures almost instantaneously. Such machines are well suited for processing data which require the repeated solution of an equation; their small size and portability place no restrictions on the time and place of their use, and programming is relatively simple. Doctors may well find programmable calculators useful in several applications, whether in research or in programming everyday calculations. The cheapest calculator of this type is the ’Sinclair Scientific Programmable’, which is supplied with several programs useful in science and technology but mostly not relevantIe medicine. Instructions for producing new programs are not supplied and it takes some time to elucidate the rules by tna, and error. We have therefore prepared programs for soliiiz

447

Fig. 1-Program for alveolar air equation.

equations related to respiratory physiology and aesthetics. Two examples are shown in figs 1 and 2.* The Sinclair scientific programmable calculator uses "reverse Polish notation"-i.e., in calculations and programs, operators (+, -, x or —) follow the variables to which they refer, no "equals" key being necessary. A program is retained until it is cleared or the machine is switched off; the memory and calculating facilities are still available when the calculator has been programmed. A maximum number of 24 steps can be handled but longer programs can be used if the execution stage is expanded to cover the extra steps. The number of steps keyed in to a program is automatically registered on the right of the display, giving an initial check that the program has been entered correctly. Execution of test some common

variables to give an expected

Rules of Program

answer

(9) Quantities in store and in the display are exchanged by x-m. (10) Quantities recalled from store by RCL or x-m can be operated upon without depressing VAR, but in some circumstances must be re-entered.

(11) When x-m is used, care is necessary to prevent quantities stored previously from re-emerging inappropriately at a subsequent execution. For example,

at

first execution and

second execution, and so on. This can be avoided either by usins STO instead of x-m or bv clearinc the disolav bv subtraction:

at

A further entry would then be

provides a further check.

preceded by VAR.

Composition

1,1 Manipulate the equation until each variable requires entry only

once during execution. storaze

This avoids of variables. For examole.

difficulty

with simultaneous

air (Vmin) and b oxygen (1/min) Dividing both numerator and denominator by b gives:

BB here a

=

=

Fig. 2--Program for Henderson-Hasselbalch equation. b : Start wtths/E and end with c/CE. 3A A vanable is entered by depressing ENTER: subsequent variables are entered byvAR. 4If storage of a variable is required from the start, depress STO to signify both entry and storage. ; operators are preceded by VAR if they act on an entered quantity.

Execution

of Programs

The numerical value of each variable, which may be real or is keyed in and the EXEC key pressed after each variable. It is important to note that the EXEC key must be depressed once for each variable referred to in the program. Thus if a mistake is made in keying in the first variable of a program containing three variables, EXEC must be used three times before restarting execution.

integer,

We thank Mrs A. M. ,

Taylor for her secretarial assistance.

Integer constants are preceded and followed by ".

-an Integer constant is ror example,

to

operate upon

a

stored

quantity use

+

REFERENCES Bet If the constant operates

on an

entered variable,

no +

is

neces-

av,

B/E/ENT/ "/3/"/x/

gives 3 a (display) -’real" quandty is required it is treated as an bv the appropriate power of ten.

’ Ar.M

a

1. 2. 3.

McWhorter, E. W. Sci. Am. 1976, 234, no. 3, p. 88. Nunn, J. F. Applied Respiratory Physiology. London, 1969, West, J. B. Ventilation/Blood Flow and Gas Exchange.Oxford, 1970.

integer mul*Copies of other programs

may be obtained from D.G.R.

Use of programmable calculator to solve physiological equations.

446 viruses, including measles. According to Zhdanov’8 and Simpson and linuma19 common R.N.A. viruses may indeed take up D.N.A. forms in tissue cultu...
226KB Sizes 0 Downloads 0 Views